Ca2+-calmodulin inhibits tail-anchored protein insertion into the mammalian endoplasmic reticulum membrane

Cytosolic components and pathways have been identified that are involved in inserting tail-anchored (TA) membrane proteins into the yeast or mammalian endoplasmic reticulum (ER) membrane. Searching for regulatory mechanisms of TA protein biogenesis, we found that Ca2+-calmodulin (CaM) inhibits the insertion of TA proteins into mammalian ER membranes and that this inhibition is prevented by trifluoperazine, a CaM antagonist that interferes with substrate binding of Ca2+-CaM. The effects of Ca2+-CaM on cytochrome b(5) and Synaptobrevin 2 suggest a direct interaction between Ca2+-CaM and TA proteins. Thus, CaM appears to regulate TA insertion into the ER membrane in a Ca2+ dependent manner. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.